Download The anti-infectives

Anti-infective
The anti-infectives
Anti-infective agents are drugs that are
designed to act selectively on foreign
organisms that have invaded and infected the
body
Anti-infectives- range from antibiotics,
antifungals, antiprotozoals, antihelmintics,
antivirals and antimycobacterial
Antibiotics
General Mechanisms of Action of AntiBacterial Agent
1. Some interfere with the biosynthesis of bacterial cell WALL
2. Some inhibit protein synthesis
3. Some change the cell membrane permeability
4. Some inhibit DNA synthesis
Spectrum of Activity of AntiBacterial Agent
◦ Narrow spectrum anti-infectives affect only a few
bacterial types.
 The early penicillin drugs are examples.
◦ Broad-spectrum anti-infectives affect many
bacteria.
 Meropenem is an example.
Because narrow spectrum antibiotics are selective, they
are more active against those single organisms than the
broad spectrum antibiotics.
Spectrum of Activity of Anti-Bacterial
oAnti-Bacterial agents that interfere with the
ability of the cell to reproduce/replicate
without killing them are called
BACTERIOSTATIC drugs.
oAntibiotics that can aggressively cause bacterial
death are called BACTERICIDAL.
oThese properties (-cidal and –static) can also
depend on the antibiotic concentration in the
blood.
Antibiotics
1.
The PENICILLINS
2.
THE CEPHALOSPORINS
3.
The Aminoglycosides
4.
The Macrolides
5.
The Lincosamides
6.
The Tetracyclines
7.
The Fluoroquinolones
8.
The Sulfonamides
The PENICILLINS
◦ Narrow spectrum penicillins
 Penicillin G
 Penicillin V
◦ Broad Spectrum Penicillins (aminopenicillin)
 Amoxicillin
 Ampicillin
 Bacampicillin
◦ Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)
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Cloxacillin
Nafcillin
Methicillin
Dicloxacillin
Oxacillin
◦ Extended-Spectrum penicillins (Anti-pseudomonal penicillins)
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Carbenicillin
Mezlocillin
Piperacillin
Ticacillin
◦ Beta-lactamase inhibitors
 Clavulanic acid
 Sulbactam
 Tazobactam
Penicillin
The structure of Penicillin
◦ Penicillin is a beta-lactam drug, with a beta-lactam ring.
The group of penicillins is called beta lactam
antibiotics.
The action of Penicillins:
The penicillin and penicillinase-resistant penicillins
produce BACTERICIDAL effects by interfering with
the ability of susceptible bacteria from biosynthesizing
the framework of the cell wall.
The bacterium will have weakened cell wall, will swell
and then burst from the osmotic pressure within the
cell.
Penicillin
Therapeutic Indications of penicillin:
◦ The penicillins are indicated for the treatment of streptococcal
infections.
Adverse Effects of Penicillins
◦ GI system effects- the major adverse effects of penicillin therapy
involve the GIT. Nausea, vomiting, diarrhea, abdominal pain,
glossitis, stomatitis, gastritis, sore mouth and furry tongue.
◦ The reason for some of these effects (superinfection) is
associated with the loss of bacterial flora.
◦ Hypersensitivity reactions- rashes, pruritus, fever. These indicate
mild allergic reaction. Wheezing and diarrhea may also occur.
Anaphylaxis can also happen leading to shock or death. It occurs
in 5-10% of those receiving penicillins.
◦ Pain and inflammation on injection sites
THE CEPHALOSPORINS
1)
First Generation cephalosporins- are largely effective against
the same gram-positive organisms affected by penicillin.
2)
Second generation cephalosporins- are effective against those
strains as well as Haemophilus influenza, Entreobacter
aerogenes and Nesseria sp. These drugs are less effective
against gram positive bacteria
3)
Third Generation cephlosporins- are relatively weak against
gram-positive bacteria but more potent against gram-negative
bacteria, to include Serratia marcescens.
4)
Fourth generation cephalosporins- are developed to fight
against the resistant gram-negative bacteria. The first drug is
cefepime.
THE CEPHALOSPORINS
 First generation cephalosporins
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cefadroxil
Cefazolin
Cephalexin
Cephalotin
Cephapirin
Cephadrine
 Second Generation cephalosporins
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Cefaclor
Cefamandole
Cefonizind
Cefotetan
Cefoxitin
Cefmetazole
Cefprozil
Cefuroxime
• Third Generation Cephaosporins
•Cefnidir
•Cefixime
•Cefoperazone
•Cefotaxime
•Cefpodoxime
•Ceftazidime
•Ceftibuten
•Moxalactam
• Fourth Generation Cephalosporin
•Cefepime
THE CEPHALOSPORINS
The mechanism of action:
 The cephalosporins are primarily BACTERICIDAL. They
interfere with the cell-wall building ability of bacteria
when they divide. They prevent the bacteria from
biosynthesizing the framework of their cell wall. The
weakened cell wall will swell and burst causing cell
death.
◦ Pharmacokinetics
 Only a few cephalosporins are administered orally, most
are administered parenterally.
 Their half-lives are short and
 they are excreted mainly in the urine.
THE CEPHALOSPORINS
Contraindications and Precautions
 The drugs are contraindicated in patients with known allergies to
cephalosporins and penicillins.
Adverse Effects
◦ GI system- Nausea, vomiting, diarrhea, anorexia, abdominal pain and
flatulence are common effects.
◦ CNS – headache, dizziness, lethargy and paresthesias have been
reported.
◦ Renal system- nephrotoxicity in individuals with pre-existing renal
disease
Drug-Drug interactions
◦ Aminoglycosides- if given with cephalosporins may increase the risk of
kidney toxicity
◦ Anti-coagulants- may experience increased bleeding tendencies .
The Aminoglycosides
The following are the aminoglycosides
1.Gentamycin
2.Tobramycin
3.Amikacin
4.Netilmicin
5.Kanamycin
Mechanism of Action:
◦ These are BACTERICIDAL. They inhibit protein
synthesis in susceptible strains of gram-negative
bacteria, leading to loss of functional integrity of the
bacterial cell membrane, which causes cell death.
Therapeutic Use of the Aminoglycosides
◦ These drugs are used to treat serious infections
caused by gram-NEGATIVE bacteria.
The Aminoglycosides
Contraindications and Precautions
◦ These drugs are contraindicated in known allergies
to aminoglycosides, in patients with renal failure,
hepatic disease, pre-existing hearing loss, myasthenia
gravis, Parkinson’s, pregnancy and lactation.
Drug to drug interactions
◦ Diuretics- increased incidence of ototoxicity,
nephrotoxicity and neurotoxicity.
◦ Anesthetics and Neuromusular blockers- increased
neuromuscular blockage and paralysis may be
possible
◦ Penicillin- synergistic action
The Aminoglycosides
Adverse Effects of Aminoglycosides
◦ CNS- irreversible deafness, vestibular paralysis, confusion, depression, disorietnation,
numbness, tingling and weakness related to drug effects.
◦ Kidney- renal toxicity, which may progress to renal failure caused by the direct
toxicity of the aminoglycosides.
◦ Hema- bone marrow depression resulting from direct drug effect may lead to
immune suppression and superinfection.
◦ GI system- nausea, vomiting, diarrhea, weight loss, stomatiits and hepatic toxicity. The
effects are due to the direct GI irritation, loss of bacterial flora and toxicity to
mucucs membrane and liver as the drugs are metabolized.
◦ Skin effects- photosensitivity, purpura, rash, urticaria and exfoliative dermatitis
◦ Cardiac- palpitaions, hypotension or hypertension
The Macrolides
The macrolides are
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Azithromycin
Clarithromycin
Dirithromycin
Erythromycin
Mechanism of Action :
The macrolides are primarily BACTERICIDAL and
sometimes bacteriostatic.
They exert their effect by binding to the bacterial cell
ribosomes and changing or altering protein
production/function.
This will lead to impaired cell metabolism and division.
The Macrolides
◦ Pharmacokinetics
 Erythromycin is destroyed by the gastric juice, which is why slats
are added to stabilize the drug. Food does not interfere with the
absorption of the macrolides.
◦ Therapeutic Use:
 These are indicated for the treatment of the following conditions:
Steptococcal infection, Mycoplasma infection, Listeria infection
and group A beta hemolytic strep infection.
◦ Contraindications and Precautions
 These agents are contraindicated in the presence of known
allergy to any macrolide, because cross-sensitivity occurs.
 Caution should be used in patients with hepatic dysfunction that
could alter the metabolism of the drug;
 in lactating women because of drug excretion in breast milk
 in pregnant women because potential adverse effects on the
developing fetus.
The Macrolides
Adverse Effects:
◦ GI system- abdominal cramping, anorexia, diarrhea, vomiting and
pseudomembranous colitis. HEPATOTOXICITY can occur if the drug is
taken in high doses with other hepatotoxic drugs.
◦ CNS- confusion, abnormal thinking and uncontrollable emotions.
◦ Hypersensitivity reactions
Drug-Drug Interactions
◦ Digoxin- increased level of dioxin can occur
◦ Anticoagulants, theophyllines and corticosteroids- increased effects of
these drugs due to impaired hepatic metabolism
◦ Astemizole- when used with macrolides, will cause fatal cardiac
arrhythmias
◦ Clindamycin or lincomycin – should not be given with erythromycin
because they compete for receptor sites.
◦ The Nursing Process and Macrolides
The Lincosamides
◦ These agents are similar to the Macrolides but
are more toxic.
◦ They are bactericidal and bacteriostatic
depending on the dose.
The following are the Lincosamides:
 Clindamycin
 lincomycin
The Mechanism of Action :
These agents penetrate the cell membrane and bind to the
ribosome in the bacterial cytoplasm to prevent the
protein production
The Lincosamides
Side effects and Adverse Reactions
◦ GIT- GI irritation, nausea, vomiting and stomatitis
◦ Allergic reactions
Drug Interactions
◦ Lincomycin and clindamycin are incompatible
with aminophyline, phenytoin, barbiturates and
ampicillin.
The Tetracyclines
The following are the tetracyclines
 Short-acting tetracyclines
 tetracycline
 oxytetracycline
 Intermediate acting tetracyclines
 demeclocycline
 methacycline
 Long acting tetracyclines
 doxycycline
 minocycline
The Mechanism of Action:
The tetracyclines inhibit protein synthesis in susceptible
bacteria leading to the inability of the bacteria to
multiply.
The Tetracyclines
Therapeutic indications of the Tetracycline
Tetracyclines are effective against a wide range of bacteria.
They are primarily BACTERIOSTATIC.
Contraindications and Precautions:
 These agents are contraindicated in the presence of
known allergy to tetrayclines.
 It is not recommended for use in pregnancy and
lactation because the drug can affect the bones and
teeth, causing permanent discoloration and sometimes
arrest of growth.
 Tetracyclines are also avoided in children less than 8
(eight) years of age because of the potential damage to
the bones and permanent discoloration of the teeth.
The Tetracyclines
◦ Adverse Effects:
◦ GI system- nausea, vomiting, diarrhea, abdominal pain, glossitis
and dysphagia.
◦ Fatal hepatotoxicity related to tetracycline’s irritating effect on
the liver cells has been reported.
◦ Musculoskletal- Tetracyclines have an affinity for teeth and bones;
they accumulate there, leading to weakening of the bone/teeth
and permanent staining and pitting.
◦ Skin- photosensitivity and rash are expected.
◦ Less frequent- bone marrow depression, hypersensitivity, super
infections, pain and hypertension
The Tetracyclines
Drug-Drug Interactions
◦ Penicillin- if taken with tetracyclines, will decrease the
effectiveness of penicillin.
◦ Oral contraceptives- if taken with tetracycline, will have
decreased effectiveness (must advise alternative methods
of contraception ).
◦ Digoxin- digoxin toxicity rises when tetracyclines are used
together
Drug-Food Interaction
◦ Dairy products- can complex with tetracycline and render
unabsorbable.
◦ Tetracyclines should then be given on an EMPTY stomach
1 hour before meals or 2-3 hours after any meal or other
medications.
The Fluoroquinolones
◦ The fluoroquinolones are broad-spectrum
antibiotics.
The examples are:
1. Nalidixic acid
2. ciprofloxacin
3. oxacillin
4. norfloxacin
5.Levfofloxacin
6.Sparfloxacin
The Fluoroquinolones
Mechanism of action
 These agents enter the bacterial cell by diffusion through cell channel.
 Once inside they interfere with the action of DNA enzymes (DNA
gyrase) necessary for the growth and reproduction of the bacteria.
 This will lead to cell death.
Therapeutic Use:
These agents are indicated for the treatment of infections caused by
susceptible strains of gram-negative bacteria including E. coli., Proteus,
pseudomonas, Strep and Staph spp
Contraindications and Precautions
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Known drug allergy to these agents contraindicate their use.
Pregnancy and lactation .
These agents are found to cause significant damage to the cartilages
such that they are given cautiously to growing children and
adolescents less than 18 years of age.
The Fluoroquinolones
Adverse Effects:
◦ CNS- dizziness, insomnia, headache, and depression related to
possible effects on the CNS membrane.
◦ GI system- nausea, vomiting, diarrhea and dry mouth related to
the direct effect on the GIT
◦ Hema- bone marrow depression related to the direct effect of
the drug on the cells of the bone marrow that rapidly turn over.
◦ Other effects- skin reactions, rash, fever and photosensitivity
Drug-Drug Interaction
◦ Iron salts, Sucralfate, mineral supplements and antacids- all of
these will decrease the effectiveness of the fluoroquinolones
◦ Quinidine, Procainamide, terfenadine, henothiazines- can prolong
the QT interval when used with the fluoroquinolones
The Sulfonamides
◦ These are called sulfa drugs that inhibit folic acid synthesis.
◦ Folic acid is necessary for the synthesis of purine and
pyrimidine precursprs of DNA and RNA. Humans cannot
produce folic acid and must obtin it form the diet. While
bacteria need to manufacture their own folic acid inside their
cell structure.
The following are the sulfonamides:
1.Sulfazalazine
2.Sulfamethoxazole
3. Sulfadiazine
4.Sulfixoxazole
The Sulfonamides
The Mechanism of Action:
 The sulfa drugs competitively block the para-amino benzoic acid to
prevent the synthesis of folic acid in susceptible bacteria that
synthesize their own folates for the production of RNA and DNA.
Therapeutic indications:
 The spectrum of activity includes the following bacteria- Chlamydia,
Nocardia, Haemophilus, E, coli and Proteus.
 Sulfa drugs are used to treat trachoma and brain abscess.
Contraindications and precautions
 These agents are contraindicated to patients with known allergy to sulfa
drugs, sulfonylureas and thiazide diuretics because they share similar
structures.
 It is not recommended for use in pregnancy because it can cross the
placenta and cause birth defects and kernicterus.
 Lactating women who take these drugs will excrete them in the breast
milk potentially causing kernicterus, diarrhea and rash in the newborn.
The Sulfonamides
Adverse Effects of the Sulfonamides
◦ GI system- nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis
and hepatic injury, which are all related to the direct irritation of the GIT
and death of normal flora.
◦ Renal system- crystalluria, hematuria and proteinuria which can progress
to a nephrotic syndrome.
◦ CNS- headache, dizziness, vertigo, ataxia, convulsions and depression
related to drug effects on the nerves
◦ Hema- bone marrow depression related to drug effects on the cells of the
bone marrow that turn over rapidly.
◦ Dermatologic effects- photosensitivity and rash and hypersensitivity
Drug-Drug Interaction
◦ Tobultamide, tolazamide, glyburide, glipizide, acetohexamide or
chlorpropamide (all are oral Anti-diabetic agents) can increase the risk of
hypoglycemia if taken with the sulfa drugs